Scientists have discovered the secrets of a sophisticated molecule that plays a role in many aspects of human health from fertility to blood pressure; digestion to mental health. This has opened up the potential for discovery of new drugs to treat an enormous variety of conditions.
In research supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust a team from the University of Cambridge shows how a molecule – the IP3 receptor – arranges itself into clusters to help broadcast vital chemical messages around cells in the form of calcium. The work is published today (25 February) in Nature.
Team leader, Professor Colin Taylor said: "Almost everything a cell does is regulated by calcium, and we know there are many diseases in both humans and animals, such as stroke or an irregular heart beat, in which calcium regulation goes wrong. But the real puzzle is trying to understand how calcium – which is amongst the simplest of all chemicals – can manage to control lots of different things at the same time. What we have found is a crucial part of that puzzle.
"Imagine you're trying to find a dancing partner at a party. You might whisper the request to several people, or you might shout it out to everyone. Some of your handful of whispered requests might be ignored and some may have you heading for the dance floor. If you shout loud enough, everyone gets to decide whether to respond. It's rather similar with messages transmitted by calcium signals: they can evoke very different responses in cells depending on whether they are whispered or shouted."
The research published today shows that when cells are stimulated, their IP3 receptors receive instructions telling them to both gather into clusters and to open and allow calcium to pass. Furthermore, IP3 receptors behave very differently when they are alone as opposed to clustered, and these differences help determine whether the calcium signal is "whispered" or "shouted".
Professor Taylor continued: "The IP3 receptors that we work on are interesting because we've found that they can both whisper and shout. Lone IP3 receptors whisper, but when they get together they can shout – not just because their combined effort is bigger, but because the calcium they release stimulates their neighbours to release calcium as well.
"We need to understand fully how IP3 receptors work if we are to begin to think of them as future targets for drugs. The clustering that we have observed fills an important gap in this understanding and takes us a step closer to being able to design drugs for a number of important diseases where we know calcium regulation goes wrong."
Professor Janet Allen, Director of Research, BBSRC said: "There is still an awful lot we don't know about the way healthy humans work. Until we get to the bottom of how complex biological processes work, what it is about them that maintains health, and where the potential points of intervention might be when things go wrong, there will be many diseases that we will not be able to treat effectively. It is reassuring to see fundamental work going on that can deliver answers to these questions. We are delighted that Professor Taylor's group have been recognised for their achievements in this area and congratulate them on publication of their Nature paper."
Contact
BBSRC Media Office
Nancy Mendoza, Tel: 01793 413355, email: nancy.mendoza@bbsrc.ac.uk
Matt Goode, Tel: 01793 413299, email: matt.goode@bbsrc.ac.uk
Notes to Editors
This work is published in the journal Nature, doi:10.1038/nature07763
CALCIUM SIGNALLING
The amount of calcium present in a cell, and where precisely it is concentrated, is incredibly important. For example, it is absolutely essential to have calcium to maintain a regular heart beat, but too much calcium can cause a cell to die – as in nerve cells during a stroke. For this second reason, cells actually work very hard to keep calcium out. It's like pumping water back across a dam and then using sluice gates to regulate its return. Cells have sluice gates for calcium called channels, some of which are altered by existing drugs for conditions such as an irregular heart beat. The IP3 receptor discussed in this paper is one of the most common calcium channels there is and it does a number of very important jobs. To date, relatively little has been found about the potential of the IP3 receptor as a drug target.
About BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £420 million in a wide range of research that makes a significant contribution to the quality of life for UK citizens and supports a number of important industrial stakeholders including the agriculture, food, chemical, healthcare and pharmaceutical sectors. BBSRC carries out its mission by funding internationally competitive research, providing training in the biosciences, fostering opportunities for knowledge transfer and innovation and promoting interaction with the public and other stakeholders on issues of scientific interest in universities, centres and institutes.
The Babraham Institute, Institute for Animal Health, Institute of Food Research, John Innes Centre and Rothamsted Research are Institutes of BBSRC. The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.
For more information see: http://www.bbsrc.ac.uk
About the Wellcome Trust
The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending over £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. http://www.wellcome.ac.uk
About the University of Cambridge
As the University of Cambridge celebrates its eight-hundredth anniversary in 2009, it is looking to the future. Its mission is to contribute to society through the pursuit of education, learning and research at the highest international levels of excellence. It admits the very best and brightest students, regardless of background, and offers one of the UK's most generous bursary schemes.
The University of Cambridge's reputation for excellence is known internationally and reflects the scholastic achievements of its academics and students, as well as the world-class original research carried out by its staff. Some of the most significant scientific breakthroughs occurred at the University, including the splitting of the atom, invention of the jet engine and the discoveries of stem cells, plate tectonics, pulsars and the structure of DNA. From Isaac Newton to Stephen Hawking, the University has nurtured some of history's greatest minds and has produced more Nobel Prize winners than any other UK institution with over 80 laureates.
Journal
Nature